Gurevich E V, Gurevich V V
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Br J Pharmacol. 2015 Jul;172(13):3229-41. doi: 10.1111/bph.13066. Epub 2015 Jun 10.
Traditional pharmacology is defined as the science that deals with drugs and their actions. While small molecule drugs have clear advantages, there are many cases where they have proved to be ineffective, prone to unacceptable side effects, or where due to a particular disease aetiology they cannot possibly be effective. A dominant feature of the small molecule drugs is their single mindedness: they provide either continuous inhibition or continuous activation of the target. Because of that, these drugs tend to engage compensatory mechanisms leading to drug tolerance, drug resistance or, in some cases, sensitization and consequent loss of therapeutic efficacy over time and/or unwanted side effects. Here we discuss new and emerging therapeutic tools and approaches that have potential for treating the majority of disorders for which small molecules are either failing or cannot be developed. These new tools include biologics, such as recombinant hormones and antibodies, as well as approaches involving gene transfer (gene therapy and genome editing) and the introduction of specially designed self-replicating cells. It is clear that no single method is going to be a 'silver bullet', but collectively, these novel approaches hold promise for curing practically every disorder.
传统药理学被定义为研究药物及其作用的科学。虽然小分子药物有明显优势，但在很多情况下已证明它们无效、易产生不可接受的副作用，或者由于特定疾病病因它们不可能有效。小分子药物的一个主要特点是其专一性：它们要么持续抑制要么持续激活靶点。正因如此，这些药物往往会引发代偿机制，导致药物耐受性、耐药性，或者在某些情况下导致敏化以及随着时间推移治疗效果丧失和/或出现不良副作用。在此我们讨论具有治疗大多数小分子药物治疗失败或无法开发的疾病潜力的新型和新兴治疗工具及方法。这些新工具包括生物制品，如重组激素和抗体，以及涉及基因转移（基因治疗和基因组编辑）和引入经过特殊设计的自我复制细胞的方法。显然，没有单一方法会是“万灵药”，但总体而言，这些新方法有望治愈几乎所有疾病。
